Real-World Outcomes of Everolimus and Exemestane for the Treatment of Metastatic Hormone Receptor-Positive Breast Cancer in Patients Previously Treated With CDK4/6 Inhibitors

Published:October 08, 2021DOI:



      Everolimus with exemestane (EVE+EXE) was FDA-approved to treat metastatic hormone receptor-positive breast cancer (mHRBC) based on BOLERO-2. However, none of those patients received prior CDK4/6 inhibitors. The purpose of this study is to evaluate the efficacy of EVE+EXE in mHRBC after CDK4/6 inhibitors.


      A retrospective review of patients ≥18 years old with mHRBC treated with EVE+EXE, for ≥30 days, at our institution from January 1, 2012, to April 1, 2020 was conducted. Primary objective was to compare progression free survival (PFS) for EVE+EXE between patients with and without prior exposure to CDK4/6 inhibitors. Secondary outcomes included overall survival and safety.


      192 patients were included in the study (n = 79, prior CDK4/6 inhibitor use; n = 113, no prior CDK4/6 inhibitor use). Baseline patient characteristics were similar between groups. Greater number of prior therapies before EVE+EXE use increased risk of disease progression (P = .017). Patients with prior CDK4/6 inhibitor use had a lower median PFS of 3.8 months (95% CI: 3.4-4.7) vs. 5.4 months (95% CI: 3.9-6.2) for patients without prior CDK4/6 inhibitor use, with a HR for progression of 1.46 (95% CI: 1.08 to 1.97, P = .013). Overall survival between groups was not significantly different.


      Patients who received a prior CDK4/6 inhibitor had a lower median PFS benefit from EVE+EXE compared to those who did not, without differences in overall survival. Although PFS is expected to decrease with subsequent lines of therapy, it is reasonable to use EVE+EXE after CDK4/6 inhibitors in selected patients, recognizing that additional benefit is modest.


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        • Baselga J
        • Campone M
        • Piccart M
        • et al.
        Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer.
        N Engl J Med. 2012; 366: 520-529
        • Piccart M
        • Hortobagyi GN
        • Campone M
        • et al.
        Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2.
        Ann Oncol. 2014; 25: 2357-2362
        • Slamon DJ
        • Neven P
        • Chia S
        • et al.
        Overall survival with ribociclib plus fulvestrant in advanced breast cancer.
        N Engl J Med. 2020; 382: 514-524
        • Im S
        • Lu Y
        • bardia A
        • et al.
        Overall survival with ribociclib plus endocrine therapy in breast cancer.
        N Engl J Med. 2019; 381: 307-316
        • Turner NC
        • Slamon DJ
        • Ro J
        • et al.
        Overall survival with palbociclib and fulvestrant in advanced breast cancer.
        N Engl J Med. 2018; 379: 1926-1936
        • Sledge Jr, GW
        • Toi M
        • Neven P
        • et al.
        The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, ERBB2-negative breast cancer that progressed on endocrine therapy – MONARCH 2.
        JAMA Oncol. 2020; 6: 116-124
      1. Cook M, Rabadi LA, Kaempf AJ, et al. Everolimus plus exemestane treatment in patients with metastatic hormone receptor-positive breast cancer previously treated with CDK4/6 inhibitor therapy. Oncologist; 26:101-106

        • Dhakal A
        • Antony Thomas R
        • Levine EG
        • et al.
        Outcome of Everolimus-Based Therapy in Hormone-Receptor-Positive Metastatic Breast Cancer Patients After Progression on Palbociclib.
        Breast Cancer. 2020; 14 (Published 2020 Jul 23)1178223420944864
      2. National Comprehensive Cancer Network (NCCN) Breast Cancer 6.2020.